Methods and systems for large spot retinal laser treatment

ABSTRACT

In some embodiments, a system for providing a therapeutic treatment to a patient&#39;s eye includes a treatment beam source configured to transmit a treatment beam along a treatment beam path. The system further includes a processor coupled to the treatment beam source, the processor being configured to direct the treatment beam onto retinal tissue of the patient&#39;s eye and deliver a series of short duration pulses from the treatment beam onto the retinal tissue at a first treatment spot to treat the retinal tissue. In some embodiments, a pre-treatment evaluation method using electroretinography (ERG) data may be used to predict effects of treatment beams at different power values and to determine optimal power values.

CROSS REFERENCE TO RELATED APPLICATION DATA

The present application claims the benefit under 35 USC § 119(e) of U.S.Provisional Appln. No. 62/725,571 filed Aug. 31, 2018; the fulldisclosure of which is incorporated herein by reference in its entiretyfor all purposes.

BACKGROUND

Therapeutic lasers are often used to treat various conditions of theeye. For example, a specific type of condition that may be treated withsuch lasers is diabetic retinopathy. Diabetic retinopathy, is damage tothe retina that is due to complications of diabetes. If left untreated,diabetic retinopathy can eventually lead to blindness. Diabeticretinopathy typically results from microvascular retinal changes. Forexample, diabetic induced effects may damage tissue of the eye, whichmay change the formation of the blood-retinal barrier and make theretinal blood vessels become more permeable. In treating suchconditions, one or more light beams may be directed into the eye and/oronto retinal tissue to cause photocoagulation of the tissue so as tofinely cauterize ocular blood vessels and/or prevent blood vessel growthto induce various therapeutic benefits. Laser photocoagulation iscommonly used for early stages of retinopathy.

In providing laser photocoagulation treatments, however, it is importantto avoid damaging sensitive tissue of the eye, such as the fovea,macula, and the like. In certain instances, it may be desired to treattissue close to or at one or more of these areas while ensuring thatdamage to such areas is avoided. Conventional laser photocoagulationtechniques may not offer optimal solutions to treating areas close to orwith such sensitive tissue while ensuring that damage to such tissuewill be avoided or greatly reduced. Further, treating relatively largeareas such as the macular region with conventional techniques such aswith a scanner or treating multiple smaller spots within the larger areamay not provide optimal, sufficient, or uniform heating to treat thearea and may result in additional loss of visual acuity. Accordingly,there is a need in the art for improved laser treatment methods andsystems including subthreshold laser photoactivation or low energy,intracellular, sub-lethal and ophthalmoscopically invisible treatment ofthe retinal tissue including the retinal pigment epithelium within themacula region for diseases such as diabetic retinopathy, central serousretinopathy, and central and branch vein occlusions, among others. Thecommon denominator for these diseases is swelling of the macula whichcauses a degradation of best corrected visual acuity. In particular,there remains a need for improved large spot laser treatment systems andmethods for treating large areas or spots of the retina including themacular region. Further, it may be desirable to treat such a large spotwith a high-powered, large beam laser such that the large spot may betreated uniformly without a scanner or otherwise treating multiplesmaller spots within the large spot.

BRIEF SUMMARY

Embodiments of the invention described herein provide systems andmethods for treating retina tissue and/or other areas of a patient'seye, in particular, large areas including the macula. Such proceduresmay be used to treat diabetic macular edema and/or other conditions ofthe eye. According to one aspect, a system for providing a therapeutictreatment to a patient's eye includes a treatment beam source configuredto transmit a treatment beam along a treatment beam path, the treatmentbeam having an infrared wavelength and a power from 1 mW to 10 W or 1 Wto 100 W. The system further includes a processor coupled to thetreatment beam source, the processor being configured to direct thetreatment beam onto retinal tissue of the patient's eye and deliver aseries of pulses from the treatment beam onto the retinal tissue at afirst treatment spot to treat the retinal tissue. The first treatmentspot is 1 to 6 mm in diameter. The duration of each pulse may besufficiently short to allow tissue cooling between pulses. This limitsthe temperature increase at the tissue and avoids inducingphotocoagulation of the retina. In contrast to photocoagulation theseeffects may be visible by means of ophthalmoscopy, optical coherencetomography, fluorescein angiography or autofluorescence imaging. Theseries of pulses directed to the treatment spot may induceintracellular, sub-lethal damage of retinal pigment epithelial cellswhich in turn activates intracellular healing mechanisms, e.g.up-regulation of heat shock proteins, cytokines and growth factors.These mechanisms restore and improve retinal pigment epithelialfunction, reduction of macular swelling and improvement ofbest-corrected-visual acuity. In some embodiments, a duration of eachpulse is sufficiently short so as to avoid inducing photocoagulation ofthe retinal tissue that results in visible tissue damage and the seriesof pulses directed to the treatment spot induces photoactivation of atherapeutic healing at the treatment spot.

In some embodiments, the treatment beam is configured to be directedonto the retinal tissue of the patient's eye to heat the tissue in asubstantially uniform manner without being scanned. The treatment beamsource may be a vertical-cavity surface-emitting laser. The treatmentbeam source may be configured to be located above the patient totransmit the treatment beam through the cornea and pupil in a generallydownward direction toward the patient's retina such that the patient maybe in a supine position during treatment. Further, the treatment beammay be configured to be directed onto 80 to 100% of the macular region.In some embodiments, the treatment beam heats the retinal tissue at thefirst treatment spot to a maximum temperature between 50 and 55 degreesC. In some embodiments, the treatment beam source may include a VCSELarray, the array comprising a set of laser-delivery elements (e.g.,laser diodes) that are individually powered. In these embodiments,delivering the series of pulses to the treatment spot may includedelivering, by the laser-delivery elements, a plurality of laser beamsto a plurality of sub-spots within the treatment spot, wherein laseroutputs of the laser-delivery elements are individually adjusted so asto ensure substantially uniform tissue heating at the treatment spot.

In certain embodiments, the system further includes an aiming beamsource configured to transmit an aiming beam along an aiming beam path,the aiming beam having a visible wavelength and the aiming beam pathextending non-coaxially relative to the treatment beam path and whereinthe processor is coupled to the aiming beam source. The processor isconfigured to direct the aiming beam onto the retinal tissue of thepatient's retina at the first treatment spot and define, via the aimingbeam, a treatment boundary surrounding the first treatment spot suchthat the first treatment spot is disposed therein. The aiming beamsource may include a vertical-cavity surface-emitting laser. Thetreatment boundary may include at least one of a ring or circularcross-section. The aiming beam may have a power under 1 mW. In certainembodiments, a convex lens is disposed between the patient and theaiming beam source configured to focus the aiming beam onto a concentricring on the retinal tissue surrounding the treatment beam at the firsttreatment spot. The treatment beam source may be disposed between theconvex lens and the aiming beam source. A concave lens may be disposedbetween the aiming beam source and the treatment beam source configuredto diverge the aiming beam around the treatment beam source such thatonly a portion of the aiming beam is blocked by the treatment beamsource.

According to another aspect, a method for providing a therapeutictreatment to a patient's retina is provided. The method includesdelivering, via a laser beam, a therapeutic treatment to retinal tissueof the patient's eye. The delivered therapeutic treatment includes atreatment spot on the retinal tissue at an intensity below that whicheffects coagulative damage in order to minimize damage to the retinaltissue. The treatment beam is delivered at an infrared wavelength, apower from 100 mW to 10 W, and along a treatment beam path and thetreatment spot ranging from 1 to 6 mm in diameter.

Conventional photocoagulation results in lethal damage by denaturing orunfolding proteins rendering them non-functional and results in visibleburns to the retina. In some embodiments, the method further includesdelivering a series of pulses from the treatment beam onto the retinaltissue at the treatment spot to therapeutically treat the retinaltissue, wherein a duration of each pulse is sufficiently short sophotocoagulation of the retinal tissue is avoided. The series of pulsesare directed to the treatment area wherein the duration of each pulse issufficiently short to allow tissue cooling between pulses. This limitsthe temperature rise at the tissue and avoids inducing photocoagulationof the retina. In contrast to photocoagulation these effects are visibleby means of ophthalmoscopy, optical coherence tomography, fluoresceinangiography or autofluorescence imaging. The series of pulses directedto the treatment spot induces intracellular, sub-lethal damage ofretinal pigment epithelial cells which in turn activates intracellularhealing mechanisms, e.g. up-regulation of heat shock proteins, cytokinesand growth factors. These mechanisms restore and improve retinal pigmentepithelial function, reduction of macular swelling and improvement ofbest-corrected-visual acuity.

In some embodiments, the therapeutic treatment is delivered only to asingle treatment spot on the retinal tissue. In some embodiments, themethod further includes heating the tissue at the treatment spot in asubstantially uniform manner without scanning the treatment beam. Insome embodiments, the treatment beam source is a vertical-cavitysurface-emitting laser.

In some embodiments, the method further includes delivering thetherapeutic treatment via a generally downward treatment beam pathtoward the patient's eye such that the patient may be in a supineposition during treatment. In some embodiments, the first treatment spotincludes a macular region of the retinal tissue. In some embodiments,the method further includes delivering the therapeutic treatment onto 80to 100% of the macular region. In certain embodiments, the methodfurther includes heating the retinal tissue at the first treatment spotto a maximum temperature between 50 and 55 degrees C.

In some embodiments, the method further includes delivering an aimingbeam from an aiming beam source along an aiming beam path, the aimingbeam having a visible wavelength and the aiming beam path extendingnon-coaxially relative to the treatment beam path, directing the aimingbeam onto the retinal tissue of the patient's eye at the first treatmentspot, and defining, via the aiming beam, a treatment boundarysurrounding the first treatment spot such that the first treatment spotis disposed therein.

In some embodiments, the aiming beam source is a vertical-cavitysurface-emitting laser. In some embodiments, the treatment boundaryincludes at least one of a ring or circular cross-section. In certainembodiments, the aiming beam has a power under 1 mW.

In some embodiments, directing the aiming beam onto the retinal tissueincludes directing the aiming beam through a convex lens disposedbetween the patient and the aiming beam source to focus the aiming beamonto a concentric ring on the retinal tissue surrounding the firsttreatment spot. The treatment beam source may be disposed between theconvex lens and the aiming beam source. Directing the aiming beam ontothe retinal tissue may include directing the aiming beam through aconcave lens disposed between the aiming beam source and the treatmentbeam source to diverge the aiming beam around the treatment beam sourcesuch that only a portion of the aiming beam is blocked by the treatmentbeam source prior to directing the aiming beam through the convex lens.

In accordance with another aspect of the invention, a system forproviding a therapeutic treatment to a patient's eye is provided thatincludes an aiming beam source configured to transmit an aiming beamalong an aiming beam path and a treatment beam source configured totransmit a treatment beam along a treatment beam path extendingnon-coaxially relative to the aiming beam path. The system includes aconvex lens disposed between the patient and the treatment beam source,a concave lens disposed between the treatment beam source and the aimingbeam source, and a processor coupled to the aiming beam source and thetreatment beam source. The processor is configured to direct the aimingbeam through the concave lens configured to diverge the aiming beamaround the treatment beam source such that only a portion of the aimingbeam is blocked by the treatment beam source prior to directing theaiming beam through the convex lens configured to focus the aiming beamonto retinal tissue of the patient's eye to define a visible treatmentboundary on the retinal tissue. The processor is configured to directthe treatment beam onto retinal tissue of the patient's eye at a firsttreatment spot disposed within the treatment boundary formed by theaiming beam.

In accordance with another aspect of the invention, a method forproviding a therapeutic treatment to a patient's eye is provided thatincludes delivering an aiming beam from an aiming beam source along anaiming beam path, the aiming beam passing through a concave lensdisposed between the patient and the aiming beam and configured todiverge the aiming beam around a treatment beam source such that only aportion of the aiming beam is blocked by the treatment beam source priorto passing through a convex lens disposed between the patient and thetreatment beam source. The method includes defining, via the aimingbeam, a visible treatment boundary on retinal tissue of the patient, theaiming beam passing through the convex lens to be focused onto theretinal tissue to define the treatment boundary. The method furtherincludes delivering, via a treatment beam from the treatment beamsource, a therapeutic treatment to retinal tissue of the patient's eyeat a treatment spot on the retinal tissue disposed within the treatmentboundary, the treatment beam being delivered along a treatment beam pathextending non-coaxial relative to the aiming beam path.

In accordance with another aspect of the invention, a method forproviding a pre-treatment evaluation of an eye of a patient. One or moresteps of the method may be performed by one or more processors. Themethod includes receiving initial electroretinography (ERG) data fromone or more ERG sensors (e.g., electrodes) positioned on a patient. Themethod may include positioning a first ERG sensor on a forehead of thepatient, and positioning a second ERG sensor below the eye. One or morefirst pulses of an optical beam may be delivered toward a retina of theeye, wherein the first pulses are set to a first power. First ERG datafrom the ERG sensors may be received, wherein the first ERG datareflects measured ERG signals generated by retinal cells as a responseto the first pulses. One or more optimal laser power values may bedetermined for performing a laser treatment. The first pulses may bedelivered to a first treatment spot on the retina, the first treatmentspot being 1 to 6 mm in diameter.

In some embodiments, the initial ERG data may reflect a baseline ERGsignal. In other embodiments, the method includes delivering one or moreinitial pulses of an optical beam toward the retina, in which case theinitial ERG data may reflect measured ERG signals generated by retinalcells as a response to the initial pulses.

In some embodiments, the method includes performing first least-squaresfits on the initial ERG data and the first ERG data to generaterespective waveforms corresponding to the initial ERG data and the firstERG data. In some embodiments, the method includes performing a secondleast-squares fit on the waveforms generated by the first least-squaresfits, wherein the second least-squares fit is configured to generate alinear representation based on the waveforms generated by the firstleast-squares fits, wherein the line describes the relationship betweenretinal temperature and laser power values. The linear representationmay be characterized by the equation C=Xβ+ε, where C is retinaltemperature, X is a power value for the treatment laser, β is aregression coefficient, and c is an error term. In some embodiments, themethod includes generating a lookup table that correlates laser powervalues to ERG signal data or retinal temperatures.

In some embodiments, the method includes delivering, by a treatment beamsource, one or more treatment laser beams to a first treatment spot onthe retina, wherein the first treatment spot is 1 to 6 mm in diameter,and wherein the treatment beam source is set to one of the optimal laserpower values. In some embodiments, the treatment beam source includes avertical-cavity surface-emitting laser (VCSEL) array, the arraycomprising a set of laser-delivery elements that are individuallypowered. In some embodiments, delivering the one or more laser beams tothe first treatment spot includes delivering, by the laser-deliveryelements, a plurality of laser beams to a plurality of sub-spots withinthe first treatment spot, wherein laser outputs of the laser-deliveryelements are individually adjusted so as to ensure substantially uniformtissue heating at the treatment spot.

In some embodiments, the method includes delivering one or more secondpulses of an optical beam toward the retina of the eye, wherein thesecond pulses are set to a second power. The method includes receivingsecond ERG data from the ERG sensors, wherein the ERG data reflectsmeasured ERG signals generated by retinal cells as a response to thesecond pulses. First least-squares fits may be performed on the initialERG data, the first ERG data, and the second ERG data to generaterespective waveforms corresponding to the initial ERG data, the firstERG data, and the second ERG data. A second least-squares fit may beperformed on the waveforms generated by the first least-squares fit,wherein the second least-squares fit is configured to generate a linearrepresentation based on the waveforms generated by the firstleast-squares fits, wherein the linear representation describes therelationship between retinal temperature and laser power values.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic illustration of a laser treatment system forproviding large spot therapeutic treatments in accordance with anembodiment of the present invention.

FIG. 2A illustrates a laser delivery system with an aiming beam source.

FIG. 2B illustrates an example of a treatment beam that includes aplurality of sub-spots within an aiming ring, wherein the treatment beamis generated by a treatment source comprising a plurality ofcorresponding laser-delivery elements.

FIG. 3 is an illustration of the laser treatment system of FIG. 1 inaccordance with yet another embodiment of the present invention.

FIG. 4A illustrates an example electroretinography (ERG) recordings of amouse retina.

FIG. 4B illustrates an example ERG recording of a human retina.

FIG. 5 illustrates an example configuration of an example ERGmeasurement system.

FIG. 6 illustrates an example process for creating a prediction modelthat may be generated prior to treatment

FIG. 7 and FIG. 8 are flowcharts illustrating example therapeutictreatment processes.

FIG. 9 is a flowchart illustrating an example method 900 providing apre-treatment evaluation of an eye of a patient.

DETAILED DESCRIPTION

Embodiments of the present invention described herein provide systemsand methods for treating retina tissue and/or other areas of a patient'seye, in particular, large areas including the macula. Such proceduresmay be used to treat diabetic macular edema and/or other conditions ofthe eye to induce one or more therapeutic benefits. In some embodiments,a series of short duration light pulses (e.g., between 5-30microseconds, 10-30 microseconds, or 5-15 microseconds) may be deliveredto the retinal tissue with a thermal relaxation time delay between eachpulse to limit the temperature rise of the target retinal tissue andthereby limit a thermal effect to only the retinal pigment epitheliallayer. Short duration pulse treatments, such as MicroPulse™ LaserTherapy of systems and devices sold by IRIDEX® Corporation (hereinaftershort duration pulse treatments of procedures), may not result invisible spots that appear on the retina and may result in less or nooverall tissue damage (e.g., visible damage). In other embodiments,photocoagulation may result in a series of visible spots that do appearin the retina.

FIG. 1 illustrates a high-level schematic of a laser delivery system 100for delivering a treatment beam to a patient's eye 110. With referenceto FIGS. 1-5, a laser delivery instrument or laser treatment system 100as described herein includes a treatment beam source 102 (e.g., a laserdelivery source) such as a laser diode (e.g., a vertical-cavitysurface-emitting laser “VCSEL”) configured to transmit a treatment beamor laser along a treatment path 124. In some embodiments, the lasertreatment system 100 may be adapted to accept a VCSEL diode in order tosignificantly reduce costs associated with the laser treatment system(VCSEL diodes may be significantly cheaper than other alternatives). Thetreatment beam source 102 may be aligned with a mirror 104 for passingor reflecting the treatment laser with low loss toward a targettreatment spot or area of a patient's eye 110 to be treated (e.g.,macula 112). Mirror 104 may be a perforated mirror, half mirror,dichroic mirror, and the like. Mirror 104 may be transparent orsemi-transparent so that some light (e.g., illumination light or aiminglaser) may be delivered back to a camera 106 as described herein. Camera106, treatment beam source 102, or an aiming beam source may be operablycoupled to a computer 109 (e.g., computing system, controller) toprovide retinal mapping, tracking, and/or imaging that may be used inthe therapeutic treatment processes described herein or to controldelivery of the treatment laser or an aiming laser. One or more lenses(e.g., identified individually as lens 108 a and lens 108 b) may beprovided to focus the reflected or passed light or laser to a targetposition (e.g., the camera 106 and/or patient's eye 110). For example,lenses 108 a and 108 b may be convex lenses.

While components of the laser treatment system 100 are illustratedseparately or externally in FIG. 1, one or more of the components (e.g.,the treatment beam source 102) may be integrated or packaged togetherinternally (e.g., within a housing of an adapter) or coupled to theadapter (e.g., via an optical fiber). The adapter or one or more of thecomponents may be coupled with a slit lamp or other ophthalmic imaginginstrument. Examples of laser delivery instruments or other variouscomponents including an adapter, controller, computer, or processor, asdescribed herein that may be provided with laser treatment system 100,in whole or in part, are described in U.S. Pat. No. 9,707,129, the fulldisclosure of which is incorporated herein by reference in its entiretyfor all purposes.

In some embodiments, the treatment beam source 102 or an aiming sourceas described in more detail below may also include a computing deviceand/or processor operably coupled to the computer 109 or other externalor internal controller to route information between the computer 109 andbeam source 102 or aiming source such that the computer 109 may controldelivery of the treatment laser or aiming laser. Computer 109 mayinclude a separate or integrated display interface including controlsand a display to display various settings and/or operations that may beadjusted by a clinician. For example, computer 109 may control treatmentbeam source 102 to deliver the treatment laser onto a target location ofthe patient's eye with desired treatment parameters or dosimetry asdescribed in more detail below. Treatment laser may be controlled to bedelivered within a defined treatment boundary, with a laser density orintensity, power, wavelength, and/or duration or pulse to treat a targetlocation of a specified size.

In some embodiments, the treatment laser may be controlled or deliveredto treat single, large target spots (e.g., macula), positions, orlocations with diameters from 1-6 mm (e.g., above 5 mm) and heat thespots uniformly (e.g., without a scanner or treating multiple smallerspots within the large spot). Such large spots may be treated with shortduration, high powered pulses from 10 mW to 10 W, 100 mW to 10 W, orfrom 1 W to 100 W (e.g., 3 W, 4 W, 5 W, above 2 W, above 5 W). Further,a duration of each pulse may be sufficiently short so as to avoidinducing traditional photocoagulation of the retinal tissue, but may besufficient to induce photoactivation or therapeutic healingsubstantially uniformly at each target position, spot, or location. Insome embodiments, the pulses may induce low energy, intracellular,sub-lethal and ophthalmoscopically invisible treatment of the retinaltissue including the retinal pigment epithelium within the macula regionfor diseases such as diabetic retinopathy, central serous retinopathy,and central and branch vein occlusions, among others. In someembodiments, tissue at the target location may be heated in a range orup to a maximum temperature from 50 to 55 degrees C. such thatphotoactivation or low energy, intracellular, sub-lethal andophthalmoscopically invisible treatment is induced while avoiding orreducing the permanent retinal damage resulting from traditionalphotocoagulation. Treatment laser may have a wavelength selected withinthe infrared spectrum (e.g., 808 nm, 810 nm). In certain embodiments,the treatment laser may be delivered to target locations toprophylactically treat the patient's eye.

FIG. 2A illustrates a laser delivery system 100 with an aiming beamsource 120. Referencing FIG. 2, in some embodiments, the laser deliverysystem 100 may include an aiming beam source 120 such as a laser diode(e.g., a vertical-cavity surface-emitting laser “VCSEL”) operablycoupled to computer 109 configured to transmit an aiming beam or laseralong an aiming path 122. In some embodiments, the aiming path 122 maynot be aligned or substantially co-axial with treatment path 124. Insome embodiments, aiming path 122 may be aligned or substantiallyco-axial with treatment path 124, as illustrated in FIG. 2. In someembodiments, as illustrated in FIG. 2, the treatment beam source 102 maybe positioned in front of or closer to the patient's eye in the path ofaiming beam source 120 such that the aiming path is partially blocked. Aconcave lens 126 may be positioned between the aiming beam source 120and treatment beam source 102 to expand or diverge the aiming laser suchthat the aiming path 122 is only partially blocked by the treatment beamsource 102. A convex lens (e.g., convex lens 108 b) may be positioned ordisposed between the treatment beam source 102 and patient's eye 110 tofocus or converge the aiming beam or treatment beam onto the target ortreatment spot on the patient's eye 110.

As illustrated, the convex lens focuses the aiming beam onto aconcentric aiming ring 130 that surrounds the treatment beam at thetreatment spot on the patient's eye such that the aiming beam is alwayslarger than the treatment beam (e.g., an incident spot 132 of treatmentbeam source 102). The aiming beam may have a wavelength in the visiblespectrum (e.g., 600 nm, 650 nm, 700 nm) to provide a visible treatmentboundary (e.g., a concentric ring, solid circular spot, or othergeometric shape) on the patient's retina with a power at or under 1 mW.The treatment boundary provided by the aiming beam provides a safetymargin for laser treatment of the eye. The treatment boundary defines anarea or periphery within which therapeutic treatment by the treatmentbeam will be or can be provided and outside which therapetuci treatmentis not provided. Further, treatment boundary provided by the aiming beammay be positioned adjacent tissue of the retina for which a therapeutictreatment is not desired (e.g., sensitive or non-target tissue). Thetissue not to be treated falls outside the treatment boundary and isvisible to a clinician. This allows the clinician to position thetreatment boundary as close to or distant from such tissue as desiredwhile ensuring that such tissue is not treated. The treatment beam isconfigured within the aiming ring or treatment boundary to ensure thattissue outside the treatment boundary is not treated accordingly.

FIG. 2B illustrates an example of a treatment beam that includes aplurality of sub-spots (e.g., the sub-spot 210 and the sub-spot 220)within an aiming ring 130, wherein the treatment beam is generated by atreatment source 102 comprising a plurality of correspondinglaser-delivery elements (e.g., an array of laser diodes). In someembodiments, the treatment laser-delivery elements may be individuallypowered to allow for fine-tuned adjustments in delivering a desiredenergy distribution. For example, each laser-delivery element in anarray may be controlled individually (e.g., by separately controllingthe pulse duration, frequency, power, etc. of each laser-deliveryelement) to cause uniform tissue heating over a region defined by thelarge spot. Such control may be necessary for uniform tissue heating,because for example, when laser-delivery elements in an array fire beamsof identical parameters toward an array of corresponding adjacentsub-spots, the tissue areas in the vicinity of the interior sub-spotstoward the center of the array of sub-spots (e.g., the sub-spot 220),may be heated more than the tissue areas in the vicinity of the exteriorsub-spots toward the periphery of the array of sub-spots (e.g., thesub-spot 210). This is due to the fact that the tissue areas near theinterior sub-spots may be exposed to and therefore accumulate compoundedenergy from a larger number of surrounding sub-spots than the tissueareas near the exterior sub-spots. The parameters of each of thesub-spots may be adjusted to control for these differences in energyexposure. For example, the treatment system may supply a relatively lowlevel of energy via the treatment laser-delivery elements correspondingto the interior sub-spots when compared to the level of energy suppliedvia the treatment laser-delivery elements corresponding to the exteriorsub-spots. As another example, the treatment system may deliver moreprecise uniformity by fine-tuned control of each of the sub-spots (e.g.,varying them to account for other variables such as tissue density). Insome embodiments, subsets of the treatment laser-delivery elements maybe powered together as groups and thereby controlled separately forsimilar reasons. For example, a 10×10 array may be divided into 10subsets of 10 elements. In this example, each of the 10 subsets may bepowered separately.

FIG. 3 illustrates an example of the laser treatment system 100 in useon a patient. In some embodiments, as illustrated in FIG. 3, the patientmay be treated with the laser treatment system 100 while in a supineposition. In such embodiments, one or more of the components of thelaser treatment system 100 may be operably coupled to a slit lamp 128,or other ophthalmic imaging system or laser delivery instrument asdescribed herein such that the treatment beam path is directed downwardonto the patient's eye. For example, a conventional slit lamp or otherophthalmic imaging instrument may be rotated about 90 degrees from aconventional position that directs the treatment into a patient's eye ina sitting position. Vertically aligning an optical axis or treatmentpath of the treatment beam source 102 improves controllability ofdistance between the treatment laser and patient's eye. Additionally,this allows for better treatment outcomes in patients, because itreduces patient head movement (e.g., by decreasing the degrees offreedom available to a patient) that may result in improper targeting ofthe treatment beam during a given treatment duration. This may beparticularly advantageous in treating children or adults with difficultysitting still. In some embodiments, the slit lamp or other instrumentmay be coupled to a ceiling or other fixture above the patient oroperating table (e.g., an IV pole or support bar). In some embodiments,additional drugs or medication may be provided during treatment of theeye (e.g., when coupled to an IV pole).

FIG. 4A illustrates an example electroretinography (ERG) recordings of amouse retina. ERG measures voltages (or biopotentials) of an electricalsignal generated by photoreceptors of a retina when they receive anexcitatory stimulus such as light (e.g., from a light source such as alaser). In some embodiments, ERG may be a noninvasive technique thatrecords an average of these generated voltages using, for example, oneor more skin-mounted sensors (e.g., electrodes). The ERG recordingillustrated in FIGS. 4A-4B depict voltages measured as a light source(e.g., a laser) is shined on a retina. ERG has been conventionallyemployed to measure retinal response to stimuli such as flashingpatterns. More information about using ERG to measure retinal responseto such external stimuli may be found in U.S. Pat. Nos. 4,874,237,5,154,174, and 9,026,189, which are hereby incorporated by referenceherein in their entirety. A recent study on mice showed that ERG signalsmay be temperature dependent in mice retinas, such that retinaltemperature of mice subjected to a laser may be inferred by a measuredERG signal. The results of this study are published in a paper—MarjaPitkanen et al., “A Novel Method for Mouse Retinal TemperatureDetermination Based on ERG Photoresponses,” Ann. Biomed. Eng., Vol. 45,No. 10, Oct. 2017—which is incorporated herein by reference in itsentirety. The ERG in FIG. 4A depicts waveforms reflecting mouse retinalERG measurements taken at a 10 ms interval for retinal temperatures of37.0 degrees C. and 40.7 degrees C. when a 532 nm laser beam is fired ata mouse retina. The electrical signal generated by the body typicallyresults in a waveform that includes two distinct waves: an a-wave 410and a b-wave 420. As shown in FIG. 4A, the ERG waveforms 430 and 440measured while at the two retinal temperatures (37.0 degrees C. and 40.7degrees C., respectively) are consistently different, indicating thatthe waveforms are temperature-dependent. As such, the waveforms may beused to infer retinal temperatures.

FIG. 4B illustrates an example ERG recording of a human retina,excerpted from Quinteros Quintana et al., “Electroretinography: ABiopotential to Assess the Function/Dysfunction of the Retina,” J.Phys.: Conf. Ser. 705 (2016), which is incorporated herein by referencein its entirety. The inventors of this disclosure observed that the ERGrecording of the human retina illustrated in FIG. 4B is very similar tothe ERG recording of the mouse retina illustrated in FIG. 4A. Forexample, the a-wave 415 maps onto the a-wave 410, and the b-wave 425maps onto the b-wave 420. This correlation led the inventors of thisdisclosure to conceive of the idea of using ERG recordings to inferhuman retinal temperature, and leveraging this property to determinetreatment parameters for laser treatments as disclosed herein.Conventional techniques for determining treatment parameters includesslowly titrating upward the power of a laser beam source until a visibleburn spot is observed on the retina to determine a maximum power valuelimit. Such techniques inevitably cause a level of damage to the retinaeven when performed correctly, which may have undesirable effects. Byits very nature, targeting the retina with a laser beam without havingestablished a maximum power value limit comes with the risk of temporaryor even irreversible damage. Additionally, the conventional techniquesrequire subjective judgments from operators that must be informed byextensive experience and skill to determine the maximum power valuelimit. Finally, assessing thresholds using these conventional techniquesrequires additional time and effort on the part of the practioner. Thepresent disclosure describes the use of an ERG measurement system foruse in conducting pre-treatment measurements for a retina in a manner soas to address the deficiencies of the conventional titration techniques.

FIG. 5 illustrates an example configuration of an example ERGmeasurement system. The illustrated ERG measurement system includes alight source 510 that is configured to aim an optical beam 515 toward aneye 110 of a patient. In some embodiments, the light source 510 may be alaser that is configured to emit a beam having a suitable wavelength(e.g., 532 nm, 577 nm, 810 nm). In some embodiments, the ERG measurementsystem includes at least two sensors (e.g., electrodes) for measuring avoltage generated by photoreceptors in response to the optical beam 515.For example, as illustrated in FIG. 5, the ERG measurement system mayinclude a first sensor 520 that is positioned on a forehead of thepatient and a second sensor 530 that is positioned below the eye 110 ofthe patient. These first and second sensors 520 and 530 may be securedto the patient via a suitable securing mechanism (e.g., adhesivepatches). A conductive cream or gel may be applied between each sensorand the patient to allow for better ERG signal acquisition. The firstand second sensors 520 and 530 may be coupled to a processor 540 (e.g.,via a wired or wireless connection) as illustrated by the arrows 525 and535, respectively. The processor 540 may perform one or more operationsas described herein to intelligently determine a model that predictscorrelations between power of the treatment laser and temperature. Forexample, the processor 540 may generate a prediction model that predictsa correlation between the power of the optical beam 515 and retinaltemperature. This prediction model may be used to predict a power thatis necessary to increase a retinal temperature to a desired amount,and/or a maximum power value limit that is configured to raise retinaltemperature to the highest amount possible without causing undue damage(e.g., in direct contrast with conventional techniques which may makeuse of visible burn spots as a routine part of the technique) to theretina. In some embodiments, the processor 540 may be coupled (e.g., viaa wired or wireless connection) to a display or other interface thatindicates these predictions to an operator (e.g., an interface thatdisplay a power range depicting the minimum and maximum power values forthe optical beam 515). In some embodiments, the processor 540 may becoupled (e.g., via a wired or wireless connection) to the light source510 (as illustrated by the arrow 545) such that the processor may beused to control the power of the light source 510. In these embodiments,the processor 540 may cause the light source 510 to direct multipleoptical beams 515 of different power values (e.g., referencing FIG. 6, aminimum power value at step 620 and the higher power at step 635) at theeye 110 to collect multiple ERG measurements and refine the predictionmodel.

ERG measurements may be particularly suitable for treatments involvinglarge spot treatments. In some embodiments, the measurable ERG responsemay be a large electrical ERG signal generated by a large number ofretinal cells. Large spot treatments may be particularly suitable forthese measurements, because they stimulate a large number of retinalcells simultaneously and thereby recruit a larger and therefore moremeasurable ERG response.

FIG. 6 illustrates an example process for creating a prediction modelthat may be generated prior to treatment (e.g., referencing FIG. 5, bythe processor 540). In some embodiments, the process may begin with aninput 610 (e.g., by the operator) to begin pre-treatment assessment of apatient eye. In some embodiments, a processor may verify that the ERGsensors and other hardware are set up correctly (e.g., by verifyingbaseline signatures received from ERG sensors), as illustrated in step615. At step 620, a laser source (or other light source) may be set to aminimum power value. At step 625 the treatment laser may be fired at arelatively low power (e.g., the minimum laser power value). In someembodiments, the steps 620 and 625 may be skipped. At step 630, ERGsignal data may be recorded (e.g., during or immediately following thefiring of the treatment laser in step 625) using sensors placed on apatient. These recorded ERG signal data may correspond to electricalresponses generated by retinal cells in response to the treatment laserat its minimum power value (or at some other relatively low power). Inembodiments where step 620 and 625 are skipped, this ERG waveform mayreflect signals detected when the eye is exposed to, for example,ambient light in which case the retinal temperature may be a baselinetemperature (e.g., 37 degrees C.). At step 635, the treatment laser maybe set to a higher power (e.g., 1 W). This higher power may be beneathan expected maximum power value limit at which damage to the retina mayoccur. At step 640, the treatment laser may be fired at the higherpower. At step 645, ERG signal data may be recorded again (e.g., duringor immediately following the firing of the treatment laser in step 635),this time corresponding to electrical responses generated by retinalcells in response to the treatment laser at the higher power. In someembodiments, the ERG waveforms may be translated from analog ERG signaldata to digital waveforms. At step 650, a processor may be used toperform a least-squares fit on the ERG signal data recorded at steps 630and 645. The least-squares fit may be performed to generate, based onthe measured ERG signal data, waveforms similar to the waveform depictedin FIG. 4B. For example, the least-squares fit may generate a waveformcorresponding to the lower-power (or baseline) ERG signal data recordedat step 630, and also a waveform corresponding to the higher-power ERGsignal data recorded at step 645. At step 655, a further these scoresfit may be performed to linearize the waveform outputs of step 650 andthereby describe a relationship between retinal temperature and a laserpower value. For example, step 655 may linearize the waveform outputs togenerate a linear representation (e.g., a single line) described by,e.g., the equation C=Xβ+ε, where C is retinal temperature, X is a powervalue for the treatment laser, β is a regression coefficient, and ε isan error term. At step 660, a lookup table may be generated based on thelinear equation of step 655. The lookup table may correlate retinaltemperatures to power values of the treatment laser such that anoperator may be able to predict a retinal temperature that may beachieved by firing a laser at a particular power. In some embodiments,any or all of the steps outlined in FIG. 6 may be performedautomatically by one or more processors. Although FIG. 6 illustratesonly two ERG measurements, the disclosure contemplates embodiments whereany suitable number of ERG measurements are performed (e.g., a series ofERG measurements performed sequentially with gradually increasing apower value of the laser). In some embodiments, a system may leverage amachine learning model that may have been trained using a large data setfrom a pool of subjects to generate more accurate prediction models. Thesubjects may be human patients, or alternatively may be animal subjectssuch as mice whose a-waves and b-waves may be correlated with a baselineERG measurement of a particular human patient to assist in generating alookup table for the particular human patient.

At step 665 of FIG. 6, a laser system 100 may be made ready fortreatment. An operator may consult the lookup table to determine one ormore optimal power values for delivering a treatment beam to a treatmentspot (e.g., a treatment spot having a diameter between 1 mm and 6 mm).As discussed previously herein, in some embodiments, the treatment beamsource may comprise a plurality of laser-delivery elements (e.g., aplurality of laser diode) that correspond to a plurality of sub-spotsthat come together to create the treatment spot. Also as discussedpreviously herein, in these embodiments, the laser output of eachlaser-delivery element (or subsets of the laser-delivery elements) maybe controlled separately and adjusted (e.g., to ensure uniform heating).In these embodiments, when an operator sets the treatment beam source ata particular power, the laser system 100 powers each laser-deliveryelement to deliver laser beams such that the sum of the power valuesdelivered by the plurality of laser-delivery elements is equal to orapproximately equal to the particular power that the operator sets. AVCSEL array (or similar arrays) may be particularly advantageous in thatit may allow for individual control of each laser-delivery element.

Using ERG measurements as described in the above-described process mayrender it unnecessary for operators to rely (or solely rely) on moreconventional techniques that involve titrating a power value of thetreatment laser upward to a maximum power value limit—for example, to apoint where a visible burn mark is created (e.g., thereby indicating themaximum power value limit). Instead, operators may use lasers at powerlevels well within a safe range to predict the effects on the eye atdifferent power levels including at the maximum power value limit.Effectively, predictions based on the ERG signal can be a substitute fora burn mark and may be recorded as suc, and processed by software. Theresult is a safer pre-treatment measurement (e.g., not requiringcreation of visible burn marks) as compared to conventional titrationtechniques. Moreover, the ERG measurement process provides reliablemeasurements of temperature by measuring retinal cellular responsesdirectly such that errors associated with other types of noninvasivemeasurements that rely on indirect measurements (e.g., measurement ofacoustic waves that are created by the pulsed laser heating of theretina that must rely on an acoustic signal that propagates throughseveral variable acoustic impedances). In addition, contrary toconventional techniques, the described ERG pre-treatment measurementprocess does not require the extensive experience and skill to makesubjective judgments. The describe ERG pre-treatment measurement processmay also be more accurate and of higher sensitivity that conventionaltechniques, because it does not rely on subjective judgments (therebyeliminating or reducing the possibility of human error). Finally, thedescribed ERG measurement process does not require the same degree oftime and effort on the part of the practioner as do conventionaltitration techniques.

In some embodiments, the ERG measurement system may be used duringtreatment of the retina to provide feedback (e.g., continuous orsemi-continuous feedback) to the operator. For example, as treatment isongoing, real-time ERG measurements may be taken and retinaltemperatures may be determined (e.g., using a lookup table generated asdescribed above during pre-treatment) and displayed to the operator toensure that the retinal temperatures do not exceed an upper limit thatwould cause permanent damage. In some embodiments, the laser treatmentsystem may include alarm system to assist the operator in preventingpermanent damage. For example, the alarm system may be coupled to theERG measurement system, and when feedback data from the ERG measurementsystem is used to determine that retinal temperatures are within athreshold of the upper limit, the alarm system may generate an alarmnotification or may even prevent operation of the treatment laser (e.g.,by disabling a foot switch or other means of operating the treatmentlaser). In some embodiments, the laser treatment system may include analarm system for ensuring that all required conditions are met before atreatment can be started. For example, the prediction model derived fromthe ERG measurement system may specify that a treatment laser is to belimited to a maximum power value limit of 3 W. In this example, if anoperator were to adjust the treatment laser to a power of 4 W, the alarmsystem may generate an alarm notification or may prevent operation ofthe treatment laser.

FIGS. 7 and 8 illustrate exemplary methods 700 and 800 for providing atherapeutic treatment to a patient's eye. One or more of any steps ofmethods described herein may be removed, re-ordered, substituted, added,or modified. At step 702, a therapeutic treatment may be delivered, viaa treatment beam from a treatment beam source, to retinal tissue of thepatient's eye 702. The delivered therapeutic treatment may include atreatment spot on the retinal tissue at an intensity below that whicheffects coagulative damage so as to minimize damage to the retinaltissue. The treatment beam is delivered at an infrared wavelength, apower from 1 to 100 W, and along a treatment beam path and the treatmentspot ranges from 1 to 6 mm in diameter. The method 800 includes, at step802, delivering an aiming beam from an aiming beam source along anaiming beam path, the aiming beam passing through a concave lensdisposed between the patient and the aiming beam and configured todiverge the aiming beam around a treatment beam source such that only aportion of the aiming beam is blocked by the treatment beam source priorto passing through a convex lens disposed between the patient and thetreatment beam source. At step 804, the method includes defining, viathe aiming beam, a visible treatment boundary on retinal tissue of thepatient, the aiming beam passing through the convex lens to be focusedonto the retinal tissue to define the treatment boundary. At step 806,the method further includes delivering, via a treatment beam from thetreatment beam source, a therapeutic treatment to retinal tissue of thepatient's eye at a treatment spot on the retinal tissue disposed withinthe treatment boundary, the treatment beam being delivered along atreatment beam path extending non-coaxial relative to the aiming beampath.

FIG. 9 illustrates an exemplary method 900 for providing a pre-treatmentevaluation of an eye of a patient. One or more of any steps of methodsdescribed herein may be removed, re-ordered, substituted, added, ormodified. At step 902, initial electroretinography (ERG) data isreceived from one or more ERG sensors positioned on a patient. At step904, one or more first pulses of an optical beam are delivered toward aretina of the eye, wherein the first pulses are set to a first power. Atstep 906, first ERG data from the ERG sensors is received, wherein thefirst ERG data reflects measured ERG signals generated by retinal cellsas a response to the first pulses. At step 908, one or more optimallaser power values are determined for performing a laser treatment.

In the description above, various embodiments of the present inventionare described. For purposes of explanation, specific configurations anddetails are set forth in order to provide a thorough understanding ofthe embodiments. However, it will also be apparent to one skilled in theart that the present invention may be practiced without the specificdetails. Furthermore, well-known features may be omitted or simplifiedin order not to obscure the embodiment being described. The subjectmatter of the present invention is described here with specificity, butthe claimed subject matter may be embodied in other ways, may includedifferent elements or steps, and may be used in conjunction with otherexisting or future technologies.

This description should not be interpreted as implying any particularorder or arrangement among or between various steps or elements exceptwhen the order of individual steps or arrangement of elements isexplicitly described. Different arrangements of the components depictedin the drawings or described above, as well as components and steps notshown or described are possible. Similarly, some features andsub-combinations are useful and may be employed without reference toother features and sub-combinations. Embodiments of the invention havebeen described for illustrative and not restrictive purposes, andalternative embodiments will become apparent to readers of this patent.Accordingly, the present invention is not limited to the embodimentsdescribed above or depicted in the drawings, and various embodiments andmodifications may be made without departing from the scope of the claimsbelow.

Other variations are within the spirit of the present invention. Thus,while the invention is susceptible to various modifications andalternative constructions, certain illustrated embodiments thereof areshown in the drawings and have been described above in detail. It shouldbe understood, however, that there is no intention to limit theinvention to the specific form or forms disclosed, but on the contrary,the intention is to cover all modifications, alternative constructions,and equivalents falling within the spirit and scope of the invention, asdefined in the appended claims.

Where a range of values is provided, it is understood that eachintervening value, to the tenth of the unit of the lower limit unlessthe context clearly dictates otherwise, between the upper and lowerlimits of that range is also specifically disclosed. Each smaller rangebetween any stated value or intervening value in a stated range and anyother stated or intervening value in that stated range is encompassed.The upper and lower limits of these smaller ranges may independently beincluded or excluded in the range, and each range where either, neitheror both limits are included in the smaller ranges is also encompassedwithin the invention, subject to any specifically excluded limit in thestated range. Where the stated range includes one or both of the limits,ranges excluding either or both of those included limits are alsoincluded.

The use of the terms “a” and “an” and “the” and similar referents in thecontext of describing the invention (especially in the context of thefollowing claims) are to be construed to cover both the singular and theplural, unless otherwise indicated herein or clearly contradicted bycontext. The term “or” in reference to a list of two or more items,covers all of the following interpretations of the word: any of theitems in the list, all of the items in the list, and any combination ofitems in the list. The terms “comprising,” “having,” “including,” and“containing” are to be construed as open-ended terms (i.e., meaning“including, but not limited to,”) unless otherwise noted. The terms“connected” or “attached” are to be construed as partly or whollycontained within, coupled to, or joined together, even if there issomething intervening. Recitation of ranges of values herein are merelyintended to serve as a shorthand method of referring individually toeach separate value falling within the range, unless otherwise indicatedherein, and each separate value is incorporated into the specificationas if it were individually recited herein. All methods described hereincan be performed in any suitable order unless otherwise indicated hereinor otherwise clearly contradicted by context. The use of any and allexamples, or exemplary language (e.g., “such as”) provided herein, isintended merely to better illuminate embodiments of the invention anddoes not pose a limitation on the scope of the invention unlessotherwise claimed. No language in the specification should be construedas indicating any non-claimed element as essential to the practice ofthe invention.

Preferred embodiments of this invention are described herein, includingthe best mode known to the inventors for carrying out the invention.Variations of those preferred embodiments may become apparent to thoseof ordinary skill in the art upon reading the foregoing description. Theinventors expect skilled artisans to employ such variations asappropriate, and the inventors intend for the invention to be practicedotherwise than as specifically described herein. Accordingly, thisinvention includes all modifications and equivalents of the subjectmatter recited in the claims appended hereto as permitted by applicablelaw. Moreover, any combination of the above-described elements in allpossible variations thereof is encompassed by the invention unlessotherwise indicated herein or otherwise clearly contradicted by context.

All references, including publications, patent applications, andpatents, cited herein are hereby incorporated by reference to the sameextent as if each reference were individually and specifically indicatedto be incorporated by reference and were set forth in its entiretyherein.

What is claimed is:
 1. A system for providing a therapeutic treatment toa patient's eye, the system comprising: a treatment beam sourceconfigured to transmit a treatment beam along a treatment beam path, thetreatment beam having an infrared wavelength and a power from 1 to 100W; an aiming beam source configured to transmit an aiming beam along anaiming beam path, the aiming beam having a visible wavelength and theaiming beam path extending non-coaxially relative to the treatment beampath; and a processor coupled to the treatment beam source and theaiming beam source, the processor being configured to: direct the aimingbeam onto the retinal tissue of the patient's eye at a first treatmentspot and define, via the aiming beam, a treatment boundary surroundingthe first treatment spot such that the first treatment spot is disposedtherein; direct the treatment beam onto retinal tissue of the patient'seye; and deliver a series of pulses from the treatment beam onto theretinal tissue at the first treatment spot to treat the retinal tissue,the first treatment spot being 1 to 6 mm in diameter, wherein: aduration of each pulse is sufficiently short so as to avoid inducingphotocoagulation of the retinal tissue that results in visible tissuedamage; and the series of pulses directed to the first treatment spotinduces photoactivation of a therapeutic healing at the first treatmentspot.
 2. The system of claim 1, wherein the treatment beam is configuredto be directed onto the retinal tissue of the patient's eye to ensuresubstantially uniform tissue heating at the treatment spot without beingscanned.
 3. The system of claim 1, wherein the treatment beam source isa vertical-cavity surface-emitting laser (VCSEL).
 4. The system of claim1, wherein the treatment beam source is configured to be located abovethe patient to transmit the treatment beam in a generally downwarddirection toward the patient's eye such that the patient may be in asupine position during treatment.
 5. The system of claim 1, wherein thefirst treatment spot comprises a macular region of the retinal tissue.6. The system of claim 5, wherein the treatment beam is configured to bedirected onto 80 to 100% of the macular region.
 7. The system of claim1, wherein the treatment beam heats the retinal tissue at the firsttreatment spot in a range of 50 to 55 degrees C.
 8. The system of claim1, wherein the treatment boundary comprises at least one of a ring orcircular cross-section.
 9. The system of claim 1, wherein the aimingbeam has a power under 1 mW.
 10. The system of claim 1, furthercomprising a convex lens disposed between the patient and the aimingbeam source configured to focus the aiming beam onto a concentric ringon the retinal tissue surrounding the treatment beam at the firsttreatment spot.
 11. The system of claim 10, wherein the treatment beamsource is disposed between the convex lens and the aiming beam source.12. The system of claim 11, further comprising a concave lens disposedbetween the aiming beam source and the treatment beam source configuredto diverge the aiming beam around the treatment beam source such thatonly a portion of the aiming beam is blocked by the treatment beamsource.
 13. The system of claim 1, wherein the aiming beam is directedonto a retinal pigment epithelium of the patient's eye.
 14. A method forproviding a therapeutic treatment to a patient's eye, the methodcomprising: delivering an aiming beam from an aiming beam source alongan aiming beam path, the aiming beam having a visible wavelength and theaiming beam path extending non-coaxially relative to a treatment beampath; directing the aiming beam onto the retinal tissue of the patient'seye at a treatment spot defining, via the aiming beam, a treatmentboundary surrounding the treatment spot such that the treatment spot isdisposed therein; and delivering, via the treatment beam from thetreatment beam source, a therapeutic treatment to retinal tissue of thepatient's eye, the delivered therapeutic treatment comprising thetreatment spot on the retinal tissue at an intensity below that whicheffects coagulative damage so as to minimize damage to the retinaltissue, the treatment beam being delivered at an infrared wavelength,and along the treatment beam path and the treatment spot being 1 to 6 mmin diameter.
 15. The method of claim 14, further comprising delivering aseries of pulses from the treatment beam onto the retinal tissue at thetreatment spot to therapeutically treat the retinal tissue, wherein aduration of each pulse is sufficiently short so as to avoid inducingphotocoagulation of the retinal tissue that results in visible tissuedamage, and wherein the series of pulses directed to the treatment spotinduces photoactivation of a therapeutic healing at that treatment spot.16. The method of claim 14, wherein the therapeutic treatment isdelivered only to a single treatment spot on the retinal tissue.
 17. Themethod of claim 14, further comprising heating the tissue at thetreatment spot in a substantially uniform manner without scanning thetreatment beam.
 18. The method of claim 14, wherein the treatment beamsource comprises a VCSEL array, the VCSEL array comprising a set oflaser-delivery elements that are individually powered, whereindelivering the treatment beam to the treatment spot comprises:delivering, by the laser-delivery elements, a plurality of laser beamsto a plurality of sub-spots within the treatment spot, wherein laseroutputs of the laser-delivery elements are individually adjusted so asto ensure substantially uniform tissue heating at the treatment spot.19. The method of claim 14, further comprising delivering thetherapeutic treatment via a generally downward treatment beam pathtoward the patient's eye such that the patient may be in a supineposition during treatment.
 20. The method of claim 14, wherein thetreatment spot comprises a macular region of the retinal tissue.
 21. Themethod of claim 20, further comprising delivering the therapeutictreatment onto 80 to 100% of the macular region.
 22. The method of claim14, wherein directing the aiming beam onto the retinal tissue comprisesdirecting the aiming beam through a convex lens disposed between thepatient and the aiming beam source to focus the aiming beam onto aconcentric ring on the retinal tissue surrounding the treatment spot.23. The method of claim 22, wherein the treatment beam source isdisposed between the convex lens and the aiming beam source.
 24. Themethod of claim 23, wherein directing the aiming beam onto the retinaltissue comprises directing the aiming beam through a concave lensdisposed between the aiming beam source and the treatment beam source todiverge the aiming beam around the treatment beam source such that onlya portion of the aiming beam is blocked by the treatment beam sourceprior to directing the aiming beam through the convex lens.
 25. Themethod of claim 14, wherein delivering the treatment beam onto theretinal tissue comprises delivering a series of pulses onto a retinalpigment epithelium at the treatment spot to therapeutically treat theretinal tissue, wherein a duration of each pulse is sufficiently shortto allow tissue cooling between pulses which limits a temperatureincrease at the tissue and avoids inducing photocoagulation of theretinal tissue that results in visible tissue damage by at least one ofophthalmoscopy, fluorescein angiography or autofluorescence imaging, andwherein the series of pulses directed to the treatment spot inducesintracellular, sub-lethal damage of retinal pigment epithelial cellswhich in turn improves retinal function.
 26. The method of claim 14,wherein the treatment beam is delivered at an intensity below that whicheffects intracellular, non-lethal damage so as to minimize damage to theretinal tissue, the treatment beam being delivered at the infraredwavelength and along the treatment beam path and the treatment spotbeing 1 mm to 6 mm in diameter.
 27. The method of claim 14, wherein thetreatment beam is delivered at a power from 100 mW to 10 W or from 1 Wto 100 W.